Variant 19-50423008-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003121.5(SPIB):c.310G>T(p.Ala104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A104P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPIB
NM_003121.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.797

Variant links:

Genes affected

SPIB (HGNC:11242): (Spi-B transcription factor) The protein encoded by this gene is a transcriptional activator that binds to the PU-box (5'-GAGGAA-3') and acts as a lymphoid-specific enhancer. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

SPIB links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14486673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPIB	NM_003121.5 linkuse as main transcript	c.310G>T	p.Ala104Ser	missense_variant	4/6	ENST00000595883.6
SPIB	NM_001243999.2 linkuse as main transcript	c.310G>T	p.Ala104Ser	missense_variant	4/6
SPIB	NM_001244000.2 linkuse as main transcript	c.252G>T	p.Leu84=	synonymous_variant	4/6
SPIB	NM_001243998.2 linkuse as main transcript	c.66+463G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPIB	ENST00000595883.6 linkuse as main transcript	c.310G>T	p.Ala104Ser	missense_variant	4/6	1	NM_003121.5	P1	Q01892-1

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151314

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000481

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000219

AC:

AN:

1372538

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

678318

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000282

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151314

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73830

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

Cadd

Benign

2.3

Dann

Benign

0.59

DEOGEN2

Benign

0.066

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

Sift4G

Benign

0.48

T;T;T

Polyphen

0.020

B;.;B

Vest4

0.21

MutPred

0.19

Gain of glycosylation at A104 (P = 0.0108);Gain of glycosylation at A104 (P = 0.0108);Gain of glycosylation at A104 (P = 0.0108);

MVP

0.48

MPC

0.024

ClinPred

0.17

GERP RS

-2.1

Varity_R

0.049

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over